The interactions between pathogenic bacteria and epithelial cells are complex and probably multifactorial. However, in vitro studies are beginning to shed light on the interactions between surface molecules on the bacteria and receptors on epithelial cells which result in adherence to and internalization of pathogenic organisms by the host cells. The exclusively human pathogen Neisseria gonorrhoeae produces a variety of opacity related proteins termed Opa. The protein OpaA specifically interacts with heparan sulfate proteoglycans on the surface of epithelial cells, and this interaction results in tight adherence of the gonococci to the cells. We have shown that in some cells, this adherence is immediately followed by internalization of the bacteria. However, in other cells, internalization requires the addition of the extracellular matrix protein vitronectin. This project uses molecular and cell biological techniques to study the ability of bacterial pathogens to utilize soluble host factors such as glycosaminoglycans and extracellular matrix proteins as a means of interacting with mammalian cells. Definition of these molecular interactions should allow the identification of novel targets for vaccination and therapeutic strategies for infectious disease.